Targeting of Natural Killer Cells by Rabbit Antithymocyte Globulin and Campath-1H: Similar Effects Independent of Specificity

T cell depleting strategies are an integral part of immunosuppressive regimens widely used in the hematological and solid organ transplant setting. Although it is known to induce lymphocytopenia, little is known about the effects of the polyclonal rabbit antithymocyte globulin (rATG) or the monoclonal anti-CD52 antibody alemtuzumab on Natural Killer (NK) cells in detail. Here, we demonstrate that induction therapy with rATG following kidney/pancreas transplantation results in a rapid depletion of NK cells. Treatment of NK cells with rATG and alemtuzumab in vitro leads to impairment of cytotoxicity and induction of apoptosis even at a 10-fold lower concentration (0.1 µg/ml) compared with T and B cells. By generating Fc-parts of rATG and alemtuzumab we illustrate that their ligation to FcγRIII (CD16) is sufficient for the significant induction of degranulation, apoptosis and inflammatory cytokine release (FasL, TNFα and IFNγ) exclusively in CD3−CD56dim NK cells whereas application of rATG and alemtuzumab F(ab) fragments abolishes these effects. These findings are of general importance as our data suggest that NK cells are also mediators of the clinically relevant cytokine release syndrome and that their targeting by therapeutic antibodies should be considered as they are functionally relevant for the effective clearance of opportunistic viral infections and anti-tumor activity posttransplantation

The Cyst-Dividing Bacterium Ramlibacter tataouinensis TTB310 Genome Reveals a Well-Stocked Toolbox for Adaptation to a Desert Environment

Ramlibacter tataouinensis TTB310T (strain TTB310), a betaproteobacterium isolated from a semi-arid region of South Tunisia (Tataouine), is characterized by the presence of both spherical and rod-shaped cells in pure culture. Cell division of strain TTB310 occurs by the binary fission of spherical “cyst-like” cells (“cyst-cyst” division). The rod-shaped cells formed at the periphery of a colony (consisting mainly of cysts) are highly motile and colonize a new environment, where they form a new colony by reversion to cyst-like cells. This unique cell cycle of strain TTB310, with desiccation tolerant cyst-like cells capable of division and desiccation sensitive motile rods capable of dissemination, appears to be a novel adaptation for life in a hot and dry desert environment. In order to gain insights into strain TTB310's underlying genetic repertoire and possible mechanisms responsible for its unusual lifestyle, the genome of strain TTB310 was completely sequenced and subsequently annotated. The complete genome consists of a single circular chromosome of 4,070,194 bp with an average G+C content of 70.0%, the highest among the Betaproteobacteria sequenced to date, with total of 3,899 predicted coding sequences covering 92% of the genome. We found that strain TTB310 has developed a highly complex network of two-component systems, which may utilize responses to light and perhaps a rudimentary circadian hourglass to anticipate water availability at the dew time in the middle/end of the desert winter nights and thus direct the growth window to cyclic water availability times. Other interesting features of the strain TTB310 genome that appear to be important for desiccation tolerance, including intermediary metabolism compounds such as trehalose or polyhydroxyalkanoate, and signal transduction pathways, are presented and discussed

Characteristics of latrines in central Tanzania and their relation to fly catches.

The disposal of human excreta in latrines is an important step in reducing the transmission of diarrhoeal diseases. However, in latrines, flies can access the latrine contents and serve as a mechanical transmitter of diarrhoeal pathogens. Furthermore, the latrine contents can be used as a breeding site for flies, which may further contribute to disease transmission. Latrines do not all produce flies, and there are some which produce only a few, while others can produce thousands. In order to understand the role of the latrine in determining this productivity, a pilot study was conducted, in which fifty latrines were observed in and around Ifakara, Tanzania. The characteristics of the latrine superstructure, use of the latrine, and chemical characteristics of pit latrine contents were compared to the numbers of flies collected in an exit trap placed over the drop hole in the latrine. Absence of a roof was found to have a significant positive association (t=3.17, p=0.003) with the total number of flies collected, and temporary superstructures, particularly as opposed to brick superstructures (z=4.26, p<0.001), and increased total solids in pit latrines (z=2.57, p=0.01) were significantly associated with increased numbers of blowflies leaving the latrine. The number of larvae per gram was significantly associated with the village from which samples were taken, with the largest difference between two villages outside Ifakara (z=2.12, p=0.03). The effect of latrine superstructure (roof, walls) on fly production may indicate that improvements in latrine construction could result in decreases in fly populations in areas where they transmit diarrhoeal pathogens